Tolerance to allopregnanolone with focus on the GABA-A receptor
Sahruh Turkmen; Torbjorn Backstrom; Goran Wahlstrom; Lotta Andreen; Inga-Maj Johansson
British Journal of Pharmacology2011
Summary (paraphrased)
Allopregnanolone is among the most potent endogenous modulators of the GABA-A receptor, and fluctuations in its levels create vulnerability to mood and emotional pathology. This review focuses on how the GABA-A receptor adapts — developing tolerance — under conditions of changing allopregnanolone exposure, such as stress, the menstrual cycle, and pregnancy. The authors describe receptor-level adaptations, including subunit changes, that alter sensitivity to neurosteroids and to GABAergic drugs. The tolerance concept is directly relevant to what happens when allopregnanolone is chronically depleted by 5-alpha-reductase inhibition and then the system must readapt after the drug is withdrawn.
Why it’s in the corpus
Supplies the receptor-plasticity mechanism that could explain why symptoms persist after allopregnanolone depletion ends — tolerance/readaptation dynamics are a prime candidate for the persistence mechanism the corpus seeks.
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